Viral hepatitis is an inflammation of the liver caused by hepatitis A, B, C, D, or E virus. All hepatitis viruses can cause acute hepatitis; further, hepatitis B, C, or D can even cause chronic hepatitis which can lead to cirrhosis, liver failure and liver cancer.
For example, in the United States, there are about 500 to 600 thousand new cases of viral hepatitis, in which hepatitis A, an acute disease caused by hepatitis A virus, accounts for 150 thousand cases. Meanwhile, there is an increase of 200 to 300 thousand new cases of hepatitis B, in which about 6 to 10% of hepatitis B cases develop into chronic hepatitis B. Chronic hepatitis B cases can easily be converted into cirrhosis, liver failure and liver cancer. It is estimated that there are about 200 to 300 million chronic hepatitis B cases throughout the world and in which the United States accounts for 1.2 million cases. Hepatitis B is caused by hepatitis B virus. Besides, there are about 150 thousand new cases of hepatitis C each year (hepatitis C was previously known as non-A non-B hepatitis). About 50 to 70% of acute hepatitis C cases are converted into chronic hepatitis C cases and chronic hepatitis C cases can easily be converted into cirrhosis, liver failure and liver cancer. It is estimated that there are about 3.5 million chronic hepatitis C cases in the United States. Both chronic hepatitis B and C cases can be converted into chronic hepatitis. Under the condition of chronic hepatitis, the hepatitis virus would continue to live and duplicate within the liver for a long period of time, which would at the same time cause chronic inflammation of the liver, leading to cirrhosis, liver failure and liver cancer.
For example, in China, there are 500 to 600 thousand new cases of viral hepatitis in which hepatitis A accounts for 150 thousand cases.
Diagnosis of viral hepatitis is based on detection of the presence of antibodies against the virus, viral genetic material, viral protein and antigen. The important biomarkers on the development of liver tissue damage derived from hepatitis is the increase in activity of blood enzymes and transaminase, such as aspartate aminotransferase (AST or S (GOT)), and alanine aminotransferase (ALT or SGPT).
The methods of treating acute and chronic hepatitis are different. For the treatment of acute viral hepatitis (hepatitis A), the first step to do is to alleviate the symptoms of nausea, vomiting and abdominal pain of the patient. Currently there is no cure for hepatitis A from the clinical perspective, and the therapy is focused on ensuring that patients have the sufficient nutritional supplements and on avoiding permanent liver injury. Patients with acute hepatitis can be treated with immunoglobulin within 2 weeks of the onset of the disease. The main treatment for chronic hepatitis B cases is interferon (interferon α-2b or interferon A) and pegylated interferon α-2a (Pegasys), as well as antiviral drugs such as telbivudine (Tyzeka), entecavir (Baraclude), lamivudine (Epivir-HBV), and adefovir dipivoxil (Hepsera). The main treatment for chronic hepatitis C cases is antivirals and interferon or interferon compound, such as pegylated interferon α-2a and pegylated interferon α-2b in combination with the antiviral drug ribavirin. Nowadays, there is no effective drug for treating liver damage caused by virus.
IL-22, also known as interleukin-10 related T cell-derived inducible factor (IL-TIF), is a glycoprotein secreted by T cells. The expression of IL-22 mRNA was originally demonstrated in IL-9-stimulated T cell lines, IL-9-stimulated mast cell line, as well as concanavalinA activated spleen cells of mouse. The human IL-22 mRNA is mainly expressed in isolated peripheral T cells and are upon stimulation by anti-CD-3 antibody or ConA. IL-22 mRNA is also expressed in the stimulated NK cells. Activated T cells are mainly CD4+ cells, especially Th1 cells via the CD28 pathway.
IL-22 precursor is composed of 179 amino acid residues (the mature peptide is composed of 146 amino acid residues). Dumoutier first reported the IL-22 DNA sequences of cloned mouse and human (Dumoutier, et al, JI 164:1814-1819, 2000). In addition, Dumoutier owned the patents related to IL-22 (U.S. Pat. No. 6,359,117 and U.S. Pat. No. 6,274,710), whereas Gurney owned the patent related to use of IL-22 in the treatment of human pancreatic disease (U.S. Pat. No. 6,551,799).
IL-22 is mainly expressed in thymus, brain, activated T cells and mast cells, the lectin-stimulated spleen cells (Duroutier JI 2002), interleukin-2/interleukin-12-stimulated NK cells (Wolk, K JI 2002), and in a number of organs and tissues, including gut, liver, stomach, kidney, lung, heart, thymus, spleen, upon LPS stimulation (Dumoutier PNAS paper), in which an increase of the expression of IL-22 in those organs and tissues can be measured.
IL-22 expresses its biological function through the combination of IL-22R1 receptor and IL-10R2 receptor. IL-22R1 is a receptor specific to IL-22 and is expressed in skin, kidney, the digestive system (pancreas, small intestine, liver, large intestine, colon), and the respiratory system (lung, bronchi). The research on IL-22 as a regulatory agent to the immune system has been published.
The medical use of IL-22 in reducing serum triglycerides and obesity has been reported in patent applications related to the medical uses of IL-22 (See WO 2006/073 508 and CN 200510023103.0).
However, it has not yet been discovered that IL-22 can play an active role in the treatment of viral hepatitis.